The Transgenic Core provides state-of-the-art generation, maintenance, and breeding of animals to Project Investigators. Centralizing these functions within a single Core derives substantial cost savings and ensures the proper, consistent and rigorous use of these approaches. First, numerous lines of transgenic and knockout mice, obtained from other laboratories, are required for the studies proposed in this Center. The Core is responsible for breeding, genotyping, and maintaining the progeny for use by the individual Projects, as well as providing the appropriate control mice. Second, new lines of transgenic and knockout mice are required for the Center Projects, will be made as part of this Core. Among these new lines are those that manipulate the expression of specific genes both temporally and spatially, in other words, inducible and cell-targeted mutations in both brain and peripheral nervous system. Our group has significant experience with these methods, which include the Estrogen Receptor/tamoxifen gene regulation system and the Cre-loxP system. A major goal of the Core is to now adapt these methods to generate state of the art targeted knockouts that will permit the most ample and controlled experimentation.